Equipment for intracerebral administration of preparations

ABSTRACT

Equipment for intracerebral administration of preparations is composed of a preparation-administering device (1) holding a preparation (2), and a plunger (4) removably arranged in the preparation-administering device adapted to push the preparation held therein toward one end of the preparation-administering device. The intracerebral preparation-administration equipment is inserted into a preparation-introducing guide (5) previously implanted in the head of a patient to introduce the preparation into its guide hole (26). The preparation is then guided to a site of administration through a flexible guide tube (23) communicated with the guide hole of the preparation-introducing guide. The equipment for intracerebral administration of preparations may be composed of a tubular preparation-retaining member (30) having a preparation contained therein, and a holder (32) for holding the tubular preparation-retaining member along with a push rod (31) inserted thereinto as an integral part thereof. In this case, the administration equipment itself is inserted into and held in the preparation-introducing guide (5).

This application is a continuation application under 37 C.F.R. §1.62 ofprior application Ser. No. 08/533,355, filed on Sep. 25, 1995, nowabandoned, which is a continuation application under 37 C.F.R. §1.62 ofprior application Ser. No. 08/142,392, filed on Nov. 24, 1993, nowabandoned.

TECHNICAL FIELD

The present invention relates to equipment for intracerebraladministration of preparations and, more particularly, an intracerebralpreparation-administering equipment for use in the medical field toadminister a preparation containing one or more drugs directly tointernal part of the brain to carry out medical treatment of the brain.

BACKGROUND ART

As is well known, functions of the living body are controlled bybioactive substances which are produced in a certain part of the livingbody and brought their ability into full play at that part. Similarly,even in the brain, the living body produces bioactive substancesrequired to control activities of the brain. Among them, there has beenknown such a bioactive substance, so-called nerve growth factor. Thisbioactive substance is a neurotrophic factor having a function to causethe cell respiration and cell differentiation of the brain and is aprotein on which people place their hopes as a material for developmentof a new medicine for senile dementias, which are becoming a problemrecently, for example, nervous degenerated diseases such as Alzheimer'sdisease, i.e., one of dementia presenilis.

As a means for carrying out administration of preparations containingthe above bioactive substance, it would be thought of using oraladministration or intravenous administration. In case of the oraladministration of bioactive substances, however, it provides almost nodrug efficacy because of decomposition in the digestive system or afirst-pass effect caused at the liver. On the other hand, in case of theintravenous administration, it is difficult to transfer the drug to theinternal part of the brain as the blood brain barriers could be a largeobstacle in passage of the drug. That is, most of the substances can notpass through blood brain barriers as blood capillaries in thesubstantive parts of the brain have inner walls covered with cells whichare poor in permeability and have such a unique structure that theseinner cells are joined together by tight junctions. In addition, theblood brain barriers, which are present between the brain and the bloodin the brain, prevent disordered transfer or distribution of ingredientsof the blood or medicines administered to or absorbed in the blood.Thus, there is such a problem that proteinaceous bioactive substancessuch as the nervous growth factor can not be transferred to the brain bythe general oral administration or intravenous administration.

Aa a solution to these problems it would be thought of (1)administration of a bioactive substance to the spinal cord, or (2)administration of a bioactive substance to the brain by craniotomy ortransforation. However, the process (1) is unsuitable for administrationof bioactive substances as braincerebrospinal barrier preventsdisordered transfer or distribution of high polymers such as protein,peptide and the like in the same manner as the blood brain barriers. Onthe other hand, the process (2) has such problems that it requiressurgical operations, that it is complex in handling, and that it wouldmake physical, psychological and economical burdens too heavy for thepatient. Further, there is a great risk of occurrence of infectiousdiseases. In addition, it is necessary to administer the bioactivesubstances at frequent intervals to improve the curative effect sincethe bioactive substances are short in half-life time even ifadministered to the internal part of the brain directly.

The problem that the repeated administration is required would be solvedto a certain extent by use of a sustained release preparation, which hasbeen proposed in Japanese patent application Ser. No. 1-208484 by someof the present inventors to extend the duration time of the bioactivesubstances. However, there still remains a problem of how to administerthe preparations to the internal part of the brain without surgicaloperations.

Separate from the above, as the most sure means for sending apreparation into the brain, there has been known an Ommaya reservoir bywhich a catheter is left in the cerebral ventricle. Although thisreservoir makes it possible to administer a preparation to the internalpart of the brain, it is impossible to supply the preparationscontinuously. In addition, it cannot be applied to preparations otherthan liquid-like preparations. Thus, this reservoir is not suitable foradministration of the preparations containing bioactive substances asthe preparation requires repeated administration because of a shorthalf-life time thereof.

DISCLOSURE OF INVENTION

Accordingly, the present invention intends to make it easy to handle anequipment as well as to make it possible to administer preparationsrepeatedly to a site of administration in a certain internal part of thebrain.

According to the present invention, the above object is achieved byproviding equipment for intracerebral administration of preparations,which comprises: preparation-administering means containing apreparation; and a plunger removably arranged in saidpreparation-administrating means for pushing the preparation out of saidpreparation-administering means toward one end thereof, said equipmentbeing adapted to be used in combination with a preparation-introducingguide previously implanted in the head of a patient.

In a preferred embodiment of the present invention, thepreparation-introducing guide is composed of a guide body having a guideholes for introducing a preparation, and a flexible guide tube connectedto a lower end of the guide body so as to communicate with the guidehole, for introducing the preparation introduced into the guide hole tothe site of application.

The above guide body has a guide hole comprising a tapered introducingpart and a cylindrical part communicated therewith, and is provided withan elastic member press-fitted in the cylindrical part of the guide holeto prevent backflow by closing the guide hole, and a cylindricalpressure member having a tapered guide hole and being fitted in saidguide hole of the guide body to fix the elastic member in place.

In another preferred embodiment, the preparation-administering means ismade in the form of a hollow needle structure. In this case, thepreparation-administrating means may be made in the form of a doubleneedle structure composed of a hollow outer needle, and an inner needleremovably arranged in the outer needle.

In another preferred embodiment, in order to allow thepreparation-administrating means to hold a preparation, thepreparation-administering equipment is provided with apreparation-holder composed of a preparation-holder body containing apreparation, and a plunger removably arranged therein, thepreparation-holder being removably attached to the outer needle of thepreparation-administrating means, whereby the preparation in thepreparationholder body is pushed in the outer needle by means of theplunger.

Further, according to the present invention, the above object isachieved by providing an equipment for intracerebral administration ofpreparations, to be used in combination with a preparation-introducingguide having a flexible guide tube for introducing a preparation loadedin a preparation-introducing guide hole to a site of application in aninternal part of the brain, said equipment comprising a tubularpreparation-retaining member including a preparation and being movablewithin the flexible guide tube of said preparation-introducing guide;and a preparation-retaining member holder capable of being inserted in aguide hole of said preparation-introducing guide.

In a preferred embodiment, the preparation-administering equipmentincludes a needle member for introducing the preparation-retainingmember into the preparation-introducing guide. Although this needlemember may be constituted only by a cylindrical member having such aninside diameter that the preparation-retaining member holder may passtherethrough, it is preferred to constitute the needle member with ahollow outer needle having an inside diameter through which thepreparation-retaining member holder may be passed, and an inner needleremovably attached to the outer needle adapted to be fitted in the guidehole of the preparation-introducing guide to determine its position.

As the preparations suitable for administration by the intracerebralpreparation-administrating equipment of the present invention, there aregiven those such as sustained release, solid preparations and semi-solidpreparations. The solid preparations may be divided, by the kind of acarrier ingredient thereof, into two groups, i.e., biodegradable solidpreparations and non-biodegradable solid preparations. The biodegradablesolid preparations include sustained release preparations containing acarrier such as collagen, gelatin, albumin, polylactic acid,polyglycolic acid, lactic acid-glycolic acid copolymer, chitin,chitosan, etc. On the other hand, the non-biodegradable solidpreparations include a carrier such as silicone, and vinyl copolymers.However, the carriers of these preparations are never limited to theabove materials. Further, the semi-solid preparations includes gel-likesemi-solid preparations.

If there is no need to take out the preparation after use because of itsdisintegration, dissolution, or decomposition in the internal part ofthe brain, the administration may be carried out by inserting theneedle-like member of the intracerebral preparation-administeringequipment into the preparation-introducing guide previously implanted inthe head so that a distal end of the guide is positioned at a site ofadministration, loading a preparation into the needle-like member, andthen operating the intracerebral preparation-administrating equipment.In this case, the preparation is introduced into and surely administeredto the site of administration through the needle-like member and thepreparation-introducing guide.

On the other hand, in case of that the preparation has to be taken outof the brain after administration because of the fact thatdisintegration, dissolution or decomposition of the preparation doesn'ttake place in the internal part of the brain, the intracerebralpreparation-administering equipment is preferably constituted by atubular preparation-retaining member, a push rod inserted in thepreparation-retaining member to hold a preparation therein on the sideof one end of the preparation-retaining member, and a holder forintegrally holding the preparation-retaining member along with the pushrod inserted therein. In this case, the push rod constituting theintracerebral preparation-administering equipment may be omittedtherefrom. By introducing the intracerebral preparation-administeringequipment into the preparation-introducing guide implanted in the headof the patient and leaving it as it is, the preparation in the distalend of the preparation-retaining member is administered to the side of acertain administration. The repeated administration can be performed bytaking the intracerebral preparation-administering equipment out of thepreparation-introducing guide after a certain time or a certain periodof time has been elapsed, and then loading another new intracerebralpreparation-administering equipment into the preparation-introducingguide. In this base, it is possible to fill up the tubularpreparation-retaining member with a semi-solid preparation as well as toobtain semipermanent curative effects, provided that the tubularpreparation-retaining member is charged with a substance producing orsecreting medicine, or bioactive substances effective for medicaltreatment of the internal part of the brain, for example, a certain kindof cells.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specific example,while indicating preferred embodiments of the invention, are given byway of illustration only, since various changes and modifications withinthe spirit and scope of the invention will become apparent to thoseskilled in the art from this detailed description.

BRIEF DESCRIPTION OF DRAWINGS

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus are not limitativeof the present invention, and wherein:

FIGS. 1(a), 1(b), 1(c) and 1(d) are sectional views of a set of anintracerebral preparation-administering equipment and apreparation-introducing guide according to the present invention;

FIG. 2 is an explanatory diagram illustrating the state of thepreparation-introducing guide of FIG. 1 that is being implanted in thehead;

FIGS. 3(a), 3(b) and 3(c) are explanatory diagrams illustrating thecondition of the intracerebral preparation-administering equipment ofFIG. 1 that is in use;

FIGS. 4(a) and 4(b) are sectional views of an intracerebralpreparation-administering equipment illustrating another embodiment ofthe present invention;

FIG. 5 is an explanatory diagram illustrating the condition of theintracerebral preparation-administering equipment of FIG. 4 that is inuse; and

FIG. 6 is an explanatory diagram illustrating still another embodimentof an intracerebral preparation administering-equipment of the presentinvention in use.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will be explained below in detail, makingreference to the accompanying drawings illustrating embodiments thereof.

An intracerebral preparation-administering equipment according to thepresent invention, shown in FIGS. 1(a)-1(d) is suitable foradministration of such preparations that they disintegrate, or dissolveor decompose in the internal part of the brain and require no removal ofthe residue. This intracerebral preparation administering equipmentcomprises a double needle 1 serving as a preparation-administratingmeans, a preparation holder 3 having a preparation 2 contained therein,and a plunger 4 for pushing out the preparation 2 loaded in the doubleneedle 1 to a site of administration. The equipment is used incombination with a preparation-introducing guide 5.

The double needle 1 comprises an outer needle 6 and an inner needle 11.The outer needle 6 is composed of a cannula 7 of a stainless steel orany other material, and a cylindrical holding member 8 for holding thecannula. The cylindrical holding member 8 is made of a plastic materialwith good biocompatibility, for example, silicone, and provided with atapered fitting hole 10 communicating with a hole 9 of the cannula 7.The inner needle 11 has a tapered projection 12 adapted to be insertedremovably into the fitting hole 10 of the outer needle 6, the projection12 is provided with a solid insertion needle 13 with a sharp pointedend. The insertion needle 13 is of a stainless steel or any othersuitable material and is so designed as to have a length such that itprotrudes beyond the distal end of the cannula 7 when the inner needle11 is inserted into the outer needle 6 completely.

The preparation holder 3 is composed of a cylindrical body 15 with atapered projection 14, and a plunger 17 produced in the form of an arrowfeather and provided at one end thereof with a push rod 16. Thepreparation holder 3 is so designed that the preparation 2 put in theholder body 15 is loaded into the preparation-introducing guide 5 byremovably inserting the projection 14 into the fitting hole 10 of theouter needle 6.

The plunger 4 is composed of a flexible rod 18 and a plunger handle 19.The plunger is so designed that it thrusts the preparation 2 to the siteof administration when the flexible rod 18 is inserted into the outerneedle 6 in use. The flexible rod 18 is required to have a flexibilityas well as the guide tube, though there is no limitation of the materialtherefor. Typical materials for the flexible rod are polymers such as,for example, polyvinyl chloride, poly-propylene, nylon 12, and Teflon(Trademark of Du Pont), and stainless steels such as SUS 316.

The preparation-introducing guide 5 comprises a guide body 20 ofsilicone, an elastic backflow check member 21, a cylindrical pressuremember 22, and a flexible guide tube 23. The guide body 20 is made ofsilicone or other material with good biocompatibility and has a taperedguide hole 20a and a cylindrical guide hole 20b communicated therewith.Fitted in the cylindrical guide hole is a guide member 24, which is madeof silicone or other plastic material with a good biocompatibility, or astainless steel. The guide member 24 provides a cylindrical recess 25and a funnel-like guide hole 26 joined thereto, the cylindrical recess25 being joined to the tapered guide hole 20a of the guide body 20. Theelastic backflow check member 21, which has a diameter slightly greaterthan that of the cylindrical recess 25, is press-fitted in cylindricalrecess 25 and fixed under pressure by the cylindrical pressure member 22to close the guide hole 26 opened at the bottom of the cylindricalrecess 25. The cylindrical pressure member 22 is made of an elasticmaterial, for example, silicone rubber.

Further, the cylindrical pressure member 22 has a trumpet-shaped guidehole 27 so as to align the cannula 7 of the double needle with the guidehole 26. The flexible guide tube 23 is attached coaxially with the guidehole 26 of the guide member 24 to a tapered projection 28 protrudingdownward from the guide body 20 and communicated with the funnel-shapedguide hole 26. The flexible guide tube 23 is formed of a plasticmaterial with a good biocompatibility, such as silicone.

Prior to use of the intracerebral preparation-administering equipment ofthe above structure, the preparation-introducing guide 25 is fixed inthe head X of a patient by surgical operation, as shown in FIG. 2. Atthat time, the distal end of the guide tube 23 of thepreparation-introducing guide 5 is fixed to the site to which thepreparation 2 is administered, i.e., the site of application, while theguide body 20 is fixed on the skull X but under the scalp Y. Thus, theguide body is marked by the external appearance of a slight swelling onthe scalp.

Further, the provision of dot lines on the external surface of the guidetube 23 makes it possible to ascertain the facts that thepreparation-introducing guide is properly located in the site ofadministration by taking X-ray photographs after or at the time ofimplantation of the preparation-introducing guide.

When making use of the above intracerebral preparation-administeringequipment, firstly, the double needle 1 is pushed into the introducingguide 5 through the scalp Y as shown in FIG. 3(a), whereby the distalend of the double needle 1 is guided towards the elastic backflow checkmember 21 through the guide hole 27 of the preparation-introducing guide5 and passed through the elastic backflow check member 21 by furtherpushing the double needle 1. After pulling the inner needle 11 out ofthe outer needle 6 of the double needle 1, the preparation holder 3 incondition shown in FIG. 1b is fitted in the fitting hole 10 of the outerneedle.

Next, the plunger 17 of the preparation holder 3 is pushed into theouter needle to load the preparation into the outer needle 6 (FIG. 3b).After pulling the preparation holder 3 out of the outer needle 6, theplunger 4 is put in the fitting hole 10 of the outer needle 6 and pushedthereinto step by step, whereby the preparation 2 is moved in the guidetube 23 of the preparation-introducing guide 5 toward the site ofadministration in the brain and administered thereto by pushing theplunger 4 to the end (FIG. 3c).

Finally, the outer needle 6 is pulled out of the preparation-introducingguide 5 along with the plunger 4 or after removal of the plunger 4. Assoon as the outer needle 6 is pulled out of the elastic member 21 of thepreparation-introducing guide 5, the bore, which has been formed in theelastic member 21 by penetration of the outer needle 6, is pushed andclosed by the elasticity of the elastic member 21. Accordingly, itprevents cerebrospinal fluid from backflow.

When a new preparation should be administered to the brain after thelapse of a certain period of time, it is sufficient to carry out theabove procedures after cutting a part of the scalp, with which thepreparation-introducing guide 5 implanted in the head is covered, bymeans of a surgical knife or the like, and inserting a double needle 1of a new intracerebral preparation-administering equipment into thepreparation-introducing guide 5.

Accordingly, the use of the intracerebral preparation-administeringequipment of the present invention makes it possible to administer thepreparations to the predetermined site of administration in the brainrepeatedly by simple procedures without performing surgical operations,provided that once a preparation-introducing guide is implanted in thehead. Further, if a preparation sustaining its drug efficacy for a longtime, for example, a sustained release preparation is used as thepreparation, there is no need to perform the administration-at frequentintervals. In addition, it will save much time and trouble required forthe medical treatment and makes it possible to reduce the risk ofinfection as well as the physical and mental pains and economical burdenof the patient.

In the foregoing embodiment, the preparation 2 is loaded into thepreparation-introducing guide 5 by the preparation holder 3, but it isnot necessarily required to use the preparation holder 3. Thepreparation may be loaded in the preparation-introducing guide 5 byplacing an aseptically packaged preparation 2 in the fitting hole 10 ofthe outer needle 6 with a pair of tweezers and then pushing it into thepreparation-introducing guide 5 by the plunger 4.

Further, in case of that a semisolid preparation is to be used as thepreparation, the administration may be carried out by use of a tubehaving such an outside diameter that it may pass through thepreparation-introducing guide. Furthermore, it is also possible toadminister a liquid-like preparation to the brain by encapsulating it ina capsule or film which dissolves quickly within the brain.

FIGS. 4(a) and 4(b) shows another embodiment of the present invention,which is so designed as to make it possible to administer a newpreparation to the brain after removal of a residual preparation when itis required to administer the preparation repeatedly because of thefacts that the preparation does not disintegrate, dissolve, or decomposein the brain. This intracerebral preparation-administering equipmentcomprises a preparation-retaining member 30 containing a preparation 2therein, a push rod 31 removably inserted in the preparation-retainingmember 30, and a holder 32 holding them as an integral part thereof.

The preparation-retaining member 30 is composed of a ultrafiltrationmembrane tube of a material with a good biocompatibility, for example, ahollow fiber membrane of polyether sulphone and closed at a distal end.The preparation-retaining member may be a tube of ethylene hexafluoride,perfluoroethylene or ethylene tetrafluoride, having perforations smallerthan the preparation. The preparation-retaining member 30 may be formedinto any size, but its size is usually determined to 0.5-1.0 mm ininside diameter and 0.8-1.5 mm in outside diameter. In order toadminister the preparation to a desired site, it is preferred to preparethe preparation-retaining member 30 with a somewhat longer than therequired length so that the preparation-retaining member can be adjustedin length by cutting it, for example, at a position illustrated in FIG.4a by a broken line, together with the push rod 31 by scissors asoccasion demands.

The push rod 31 is made of a flexible material such as nylon, silicone,polytetrafluoroethylene, polyacetal, ethylene tetrafluoride and the likein the form of a rod with a diameter equal to or slightly smaller thanthe inside diameter of the preparation-retaining member 30, and adjustedto be suitable for keeping the preparation 2 loaded in thepreparation-retaining member 30 at a distal end thereof. The push rod ismade of a material softer than that of the flexible guide tube since itis required to move it back and forth together with thepreparation-retaining member 30 within the flexible guide tube 23 alongthe entire length thereof without causing displacement of the flexibleguide tube 23.

The holder 32 is composed of a tubular holder body 33, a holding ring 34of an elastic material such as silicone rubber, a pressure ring 35 of arelatively hard material such as silicone resin, and a tubular fixingmember 36. The preparation-retaining member 30, which has beenpreviously equipped with the preparation 2 and the push rod 31, isinserted into the holding ring 34 and pressure ring 35, and theninserted from the distal end thereof into the body 33. The fixing member36 is then screwed in a threaded hole of the proximal end of the body 33to press the holding ring 34 toward the body, whereby the holding ring34 is compressed and deformed to fix the preparation-retaining member 30in place (cf. FIG. 4b).

The intracerebral preparation-administering equipment with the abovestructure is used in combination with a preparation-introducing guide 5previously implanted in the head, in the same manner as that of theembodiment of FIG. 1. In this case, the preparation-introducing guide 5is, as shown in FIG. 5, composed of a guide body 20 of silicone resinand a flexible guide tube 23. The guide body 20 has a guide hole 37including a tapered portion 37a and a cylindrical portion 37b joinedthereto, and the cylindrical portion 37b of the guide hole 37 iscommunicated with the guide tube-mounting hole 38 which passes throughthe tapered projection 28 formed as an integral part of the lowerportion of the guide body 20. Within the mounting hole 38, the flexibleguide tube 23 is arranged coaxially with the guide hole 37.

In use, the preparation-retaining member 30, which has been previouslyprovided with the preparation 2 and the push rod 31, is cut at a pointcorresponding to a length up to the site of administration. This lengthis determined by taking an X-ray photograph of thepreparation-introducing guide 5 which was previously fixed in the headof the patient by surgical operation. Then, the preparation-retainingmember 30 is fixed in the holder 32 to complete the intracerebralpreparation-administering equipment. The preparation-retaining member 30is inserted into the guide hole 37 of the preparation-introducing guide5 through the scalp Y cut with a surgical knife until the holder 32 isreceived into the guide hole 37 of the preparation-introducing guide 5,thereby the preparation 2 held in the preparation-retaining member 30 isput in place in the brain and the guide hole of thepreparation-introducing guide 5 is closed by the holder 32 to preventthe backflow of the cerebrospinal fluid. In order to make a sure sealbetween the holder 32 and the guide hole 37, it may be possible toprovide a seal ring between the holder body 33 and fixing member 36.

By leaving the thus introduced preparation-administering equipment as itis, the preparation 2 in the preparation-retaining member dissolvesgradually in the fluid infiltrating into the ultrafiltration tubeconstituting the preparation-retaining member 30, and is thenadministered to the site of administration in the brain by osmosis.After leaving intracerebral preparation-administering equipment for acertain period of time, the scalp Y is cut open with a surgical knife sothat the preparation-retaining member 30 may pass through the opening.Then, the preparation-retaining member 30 is pulled out of thepreparation-introducing guide 5 so as to complete the administration,using an extracting metal part 40 which has a threaded lower end adaptedto be screwed into the threaded bore 39 of a head portion of the fixingmember 36 of the holder 32. This is done by inserting the extractingmetal part 40 into the preparation-introducing guide 5, screwing it intothe threaded bore 39 of the head portion of the holder 32, and thenextracting the extracting metal part 40 from the preparation-introducingguide 5. If necessary, a holder 32 provided with a newpreparation-retaining member 30 containing a preparation may be insertedinto the preparation-introducing guide 5.

With the intracerebral preparation-administrating equipment of the aboveembodiment, it is possible to administer the preparation to the site ofadministration surely. Further, if the release of the drug has beencompleted or if the administration of the preparation is to be stopped,the residue or residual preparation can be collected by extracting thepreparation-retaining member from the site of administration.

FIG. 6 shows still another embodiment of the intracerebralpreparation-administering equipment according to the present invention,which enables to perform intracerebral administration of preparationsrepeatedly, when the preparation does not or insufficientlydisintegrate, dissolve, or decompose in the brain, by administer a newpreparation to the brain after taking a residual preparation out of thesite of administration, like the embodiment of FIG. 4. Thisintracerebral preparation-administering equipment further comprises adouble needle 41 in addition to parts of the administering equipmentshown in FIG. 4. The double needle 41 is composed of a cylindrical outerbarrel 42 and an inner needle 43 removably arranged in the outer barrel42. The inner needle 43 is tapered at a distal end 43a thereof andadapted to be removably inserted into the guide hole 37 of thepreparation-introducing guide 5.

In use, the preparation-retaining member 30, into which a preparation 2and a push rod 31 have been previously loaded, is cut at a pointcorresponding to a length up to the site of administration and thenfixed to the holder 32 to assemble a preparation-retaining member set.Then, the scalp Y is cut with a surgical knife at an area over thepreviously implanted preparation-introducing guide 5, and the doubleneedle 41 is inserted into the guide hole 37 of thepreparation-introducing guide 5 through the scalp. After the doubleneedle 41 is put in place by inserting it until the flanged portion 42aof the outer barrel 42 comes into contact with the scalp as indicated bya broken line in FIG. 6, the inner needle 43 is pulled out of the outerbarrel 42 and then the preparation-retaining member 30 is inserted intothe preparation-introducing guide 5 through the outer barrel 42 untilthe holder 32 is received in the guide hole 37 of thepreparation-introducing guide 5, thereby the preparation is held inplace in the brain. After this, the outer barrel 42 is removed from thepreparation-introducing guide 5 and the scalp is stitched with asurgical needle to complete the administration procedures.

When the preparation-retaining member 30 has to be taken out of thepreparation-introducing guide 5 after leaving it for a certain time or acertain period of time, this may be done by cutting the scalp open witha surgical knife so that the preparation-retaining member holder 32 maypass therethrough, inserting a double needle 41 into thepreparation-introducing guide 5 until the flanged portion 42a of theouter barrel 42 comes into contact with the scalp, pulling the innerneedle 43 out of the outer barrel 42, screwing the extracting metal part40 in the preparation-retaining member holder 32 through the outerbarrel 42, and then pulling them out of the preparation-introducingguide 5. If necessary, a new preparation-retaining member set with a newpreparation may be inserted into the preparation-introducing guide 5.

Even in this embodiment, the intracerebral preparation-administratingequipment makes it possible to administer the preparation to the desiredsite surely, without performing surgical operations, when used incombination with the preparation-introducing guide previously implantedin the head. Further, if the release of the drug has been completed orif the administration of the preparation is to be stopped, the residueor preparation can be collected by extracting the preparation-retainingmember from the preparation-introducing guide.

The invention being thus described, it will be obvious that the same maybe varied in many ways. Such variations are not to be regarded as adeparture from the spirit and scope of the invention, and all suchmodifications as would be obvious to one skilled in the art are intendedto be included within the scope of the following claims.

We claim:
 1. Equipment for intracerebral administration of preparationscomprising:a preparation-introducing guide implantable in the head of apatient; preparation-administrating means for inserting a solid orsemi-solid preparation through the preparation-introducing guide; aflexible plunger insertable into and readily removable from thepreparation-administrating means; said preparation-introducing guidecomprising a guide body with a guide hole passing therethrough forintroducing preparations, the guide body including an upwardly protrudedhead portion which causes a slight swelling of a scalp of the patientand a downwardly protruded tapered projection, backflow check means forpreventing a cerebrospinal fluid from backflowing when saidpreparation-introducing guide is implanted in the head of a patient,said backflow check means being arranged in the guide hole of said guidebody to close said guide hole; and a flexible guide tube connected tothe downwardly protruded tapered projection of said guide body andcommunicated with said guide hole to introduce the preparation into asite of administration, the preparation-administrating means including ahollow needle at one end and an inner needle removably inserted intosaid hollow needle, the hollow needle being insertable into and readilyremovable from the preparation-introducing guide, the flexible plungerbeing inserted into said preparation-administrating means after removingsaid inner needle from the hollow needle and loading a preparation intothe preparation-administrating means to push the preparation to a siteof administration through said preparation-introducing guide.
 2. Theequipment for intracerebral administration of preparations claimed inclaim 1, wherein said preparation-administrating means further includesa preparation holder comprising a preparation holder body and a loadingplunger, the preparation holder body holding a solid or semi-solidpreparation therein and being detachably mounted to the hollow needleafter removing the inner needle from the hollow needle, thepreparation-loading plunger being detachably mounted in said holder bodyand loading the preparation into the preparation-introducing guidethrough the hollow needle.
 3. The equipment for intracerebraladministration of preparations claimed in claim 1, wherein at least thehollow needle is insertable through the backflow check means.
 4. Theequipment for intracerebral administration of preparations claimed inclaim 3, wherein the backflow check means has a diameter slightlygreater than the guide hole such the backflow check means ispress-fitted in the guide hole, at least the hollow needle beinginsertable through the backflow check means to form a bore therein suchthat the preparation is passed therethrough to the site ofadministration, the backflow check means closing the bore uponwithdrawal of the hollow needle to thereby close the guide hole and sealthe preparation-introducing guide from ambient environment.
 5. Theequipment for intracerebral administration of preparations claimed inclaim 3, wherein the backflow check means is initially without anyopenings to thereby close the guide hole and seal thepreparation-introducing guide from ambient environment.
 6. The equipmentfor intracerebral administration of preparations claimed in claim 1,wherein the hollow needle of the preparation-administrating means hasone of the inner needle, a preparation holder and the flexible plungerinserted therein,with the inner needle inserted into the hollow needle,the preparation-administering means initially engages thepreparation-introducing guide, a preparation being inserted into thepreparation-introducing guide when the preparation holder is insertedinto the hollow needle, the preparation-introducing guide having apreparation-administering plunger for pushing the preparation from thepreparation holder into and out of the hollow needle, and the flexibleplunger being inserted into the hollow needle to push the preparationthrough the preparation-introduction guide, the inner needle, thepreparation holder and the flexible plunger all only being sequentiallyinsertable into the hollow needle and all being readily detachable fromthe hollow needle.
 7. Equipment for intracerebral administration ofsolid or semi-solid preparations, for use in combination comprising:apreparation-introducing guide implantable in the head of a patient;preparation-retaining means having a solid or semi-solid preparationtherein and being held in the preparation-introducing guide implanted inthe head of a patient to administer a preparation, saidpreparation-introducing guide comprising a guide body, backflow checkmeans for preventing a cerebrospinal fluid from backflowing, and guidetube means for guiding the preparation introduced into said guide holeto an objective site in a brain, said guide body having a guide holepassing therethrough for introducing preparations and including anupwardly protruded head portion which causes a slight swelling of ascalp of the patient and a downwardly protruded tapered projection, saidguide hole including a tapered guide hole and a cylindrical guide holecommunicated therewith, said backflow check means being arranged in thecylindrical guide hole of the guide body to close said guide hole whensaid preparation-introducing guide is implanted in the head of apatient, the guide tube means being a flexible guide tube inserted inthe downwardly protruded tapered projection of the guide body andcommunicated with the guide hole to introduce the preparation into asite of administration; said preparation-retaining means comprising atubular preparation-retaining member having a preparation therein, thetubular preparation-retaining member being freely movable within theflexible guide tube of said preparation-introducing guide, thepreparation-retaining means further includes a needle member forintroducing the tubular preparation-retaining member into thepreparation-introducing guide; and a holder for holding saidpreparation-retaining member, said holder surrounding an end of thepreparation-retaining member and being insertable into and fixable inthe guide hole of said preparation-introducing guide, the holderconstituting the backflow check means when inserted in said guide holeof said introducing guide.
 8. The equipment for intracerebraladministration of preparations claimed in claim 7, wherein said needlemember has a double needle structure composed of an outer tube and aninner needle, said outer tube having an inside diameter through whichsaid holder with preparation-retaining means may be passed.
 9. Theequipment for intracerebral administration of preparations claimed inclaim 7, wherein said preparation-retaining means has a structure whichpermits diffusion and release of a drug contained in the preparationheld therein.
 10. The equipment for intracerebral administration ofpreparations claimed in claim 7, wherein the tubularpreparation-retaining member is composed of a ultrafiltration membrane.11. The equipment for intracerebral administration of preparationsclaimed in claim 7, further including a slender push rod of a flexiblematerial removably inserted into the tubular preparation-retainingmember.
 12. The equipment for intracerebral administration ofpreparations claimed in claim 7, wherein said backflow check means is anelastic backflow check member press-fitted in said guide hole to closethe guide hole, said backflow check member being fixed by a cylindricalpressure member fitted in said guide hole.
 13. The equipment forintracerebral administration of preparations claimed in claim 7, whereinthe holder comprises a holder body, at least one ring and a fixingmember, the tubular preparation-retaining member extends from a forwardend of the holder body, the at least one ring engages the tubularpreparation-retaining member inside the holder body and the fixingmember presses the at least one holding ring toward the forward end ofthe holder body to hold the tubular preparation-retaining member withinthe holder body.
 14. The equipment for intracerebral administration ofpreparations claimed in claim 7, wherein the backflow check means has adiameter slightly greater than the guide hole such the backflow checkmeans is press-fitted in the guide hole, the needle being insertablethrough the backflow check means to form a bore therein such that thepreparation is passed therethrough to the site of administration, thebackflow check means closing the bore upon withdrawal of the needle tothereby close the guide hole and seal the guide tube from ambientenvironment.
 15. The equipment for intracerebral administration ofpreparations, claimed in claim 7, wherein the backflow check means isinitially without any openings to thereby close the guide hole and sealthe guide tube from ambient environment.
 16. The equipment forintracerebral administration of preparations claimed in claim 7, whereinsaid holder is composed of a tubular holder body, a holding ring, apressure ring of a relatively hard material, and a tubular fixingmember.
 17. The equipment for intracerebral administration ofpreparations claimed in claim 7, further comprising a push rod removablyinsertable into the tubular preparation-retaining member and whereinsaid tubular preparation-retaining member is composed of aultrafiltration membrane of a good biocompatible material, and whereinsaid push rod is of a flexible material softer than that of the flexibleguide.
 18. The equipment for intracerebral administration ofpreparations claimed in claim 7, wherein the preparation in the tubularpreparation-retaining member is at an end of the member opposite to theend surrounded by the holder.
 19. The equipment for intracerebraladministration of preparations claimed in claim 18, wherein the tubularpreparation-retaining member is insertable into and through the guide toposition the preparation in the end of the tubular preparation-retainingmember outside the guide adjacent to the objective site in the brain.